Use of different combination diphtheria-tetanus-acellular pertussis vaccines does not increase risk of 30-day infant mortality. A population-based linkage cohort study using administrative data from the Australian Childhood Immunisation Register and the National Death Index.

Objective

To determine whether differences in combination DTaP vaccine types at 2, 4 and 6?months of age were associated with mortality (all-cause or non-specific), within 30?days of vaccination.

Infective Endocarditis Due to Treponema pallidum: A Case Diagnosed Using Polymerase Chain Reaction Analysis of Aortic Valve

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Syphilitic aortitis might coexist in a dysfunctional aortic valve, but the etiology remains unclear, because microbiological diagnosis is difficult. A 62-year-old man with low-grade fever was diagnosed with aortitis and infective endocarditis, due to Treponema pallidum infection, using polymerase chain reaction analysis. This case suggests that syphilis might cause infective endocarditis.     

Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.     

Factors associated with clinically significant hypoglycemia in patients with type 1 diabetes using sensor-augmented pump therapy with predictive low-glucose management: A multicentric study on iberoamerica

Background and aimsDespite using sensor-augmented pump therapy (SAPT) with predictive low-glucose management (PLGM), hypoglycemia is still an issue in patients with type 1 Diabetes (T1D). Our aim was to determine factors associated with clinically significant hypoglycemia (<54 mg/dl) in persons with T1D treated with PLGM-SAPT.Methodology: This is a multicentric prospective real-life study performed in Colombia, Chile and Spain. Patients with T1D treated with PLGM-SAPT, using sensor ≥70% of time, were included. Data regarding pump and sensor use patterns and carbohydrate intake from 28 consecutive days were collected. A bivariate and multivariate Poisson regression analysis was carried out, to evaluate the association between the number of events of <54 mg/dl with the clinical variables and patterns of sensor and pump use.Results188 subjects were included (41 ± 13.8 years-old, 23 ± 12 years disease duration, A1c 7.2% ± 0.9). The median of events <54 mg/dl was four events/patient/month (IQR 1–10), 77% of these events occurred during day time. Multivariate analysis showed that the number of events of hypoglycemia were higher in patients with previous severe hypoglycemia (IRR1.38; 95% CI 1.19–1.61; p < 0.001), high glycemic variability defined as Coefficient of Variation (CV%) > 36% (IRR 2.09; 95%CI 1.79–2.45; p < 0.001) and hypoglycemia unawareness. A protector effect was identified for adequate sensor calibration (IRR 0.77; 95%CI 0.66–0.90; p:0.001), and the use of bolus wizard >60% (IRR 0.74; 95%CI 0.58–0.95; p:0.017).ConclusionIn spite of using advanced SAPT, clinically significant hypoglycemia is still a non-negligible risk. Only the identification and intervention of modifiable factors could help to prevent and reduce hypoglycemia in clinical practice.     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

Who should do endovascular repair of complex aortic aneurysms and how should they do them?

BackgroundCure of aneurysms which involve the aorta at the level of the visceral arteries and the thoracoabdominal segment remains a considerable surgical enterprise with a relatively high mortality and morbidity despite improvements of the surgical procedure and anesthetic technique. Fenestrated and branched endovascular stent grafts are currently available offering an attractive less invasive option especially for most frail patients. These grafts are relatively recent, technically more demanding to insert than the current stent graft for infrarenal aneurysm and besides, given the relative low frequency of the disease, they are much less used by practitioners. Thus, unconditional widespread of this sophisticated technique may not necessarily benefit patients.MethodsWe reviewed our experiences and articles regarding this concern, 1) who should perform this new technique and 2) in what kind of setting.ConclusionBased on the combined complexities of 1) patients selection, 2) proper planning and manufacturing of the graft, 3) the need for outstanding imaging and operating facilities, 4) and the required endovascular skill of physicians involved in the procedure, we feel that only highly specialized centers should be allowed to perform this complex procedure.     

Residential Greenness Alters Serum 25(OH)D Concentrations: A Longitudinal Cohort of Chinese Older Adults

ObjectivesVitamin D deficiency is prevalent among older adults. We aimed to study whether residential greenness could alter serum 25(OH)D concentrations as a possible mechanism of residential greenness's positive health effects.DesignA longitudinal cohort study.Setting and ParticipantsWe included older adults aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) with follow-up between 2012 and 2014.MethodsWe measured residential greenness by calculating annual average Normalized Difference Vegetation Index (NDVI) in a 500 m radius by using satellite images around each participant's residential address. Serum 25-hydroxyvitamin D (25(OH)D) concentration was dichotomized into 2 categories: nondeficiency (≥50 nmol/L) and deficiency (<50 nmol/L). We used the generalized estimating equation to examine the relationship between annual average NDVI and serum 25(OH)D.ResultsWe included 1336 participants in our analysis. The annual average NDVI was 0.49, and mean serum 25(OH)D was 43 nmol/L at baseline. Each 0.1-unit increase in annual average NDVI was associated with a 13% higher odds of vitamin D nondeficiency [95% confidence interval (CI): 1.01, 1.26]. The association was stronger among men [odds ratio (OR): 1.17, 95% CI: 1.02, 1.35] than women (OR: 1.08, 95% CI: 0.91, 1.29) and also stronger among those who were free of activities of daily living (ADL) disability at baseline (OR: 1.12, 95% CI: 1.00, 1.25). During the follow-up period, the participants who lived in greener areas were more likely to have an improved, rather than stable or deteriorated, vitamin D status (OR: 1.94, 95% CI: 1.51, 2.51).Conclusions and ImplicationsOur study suggests that higher levels of residential greenness are associated with higher serum 25(OH)D concentrations, which has implications for prevention of vitamin D deficiency among older adults.